Hepatitis A Virus

Picornaviridae family One serotype- stable(protective for life) Non-enveloped Single stranded positive Stable ( ether, acid, heat: 60 c for 1 hr) Destroyed (autoclaving, boil 5 min, chlorine)

 Feco-oral route Crowded: early age, high sanitation: older Clinical finding IP: 3-4 weeks Asymptomatic in children Life long immunity No chronicity

Lab investigation
Detect HAV antibodies IgM: acute phase (most reliable) IgG: life long protection Detect HAV antigen in stool (ELISA) Detect HAV RNA in stool (PCR, nucleic acid hybridization)

Prevention and control

Control food and water Good hygiene-hand refreshing Chlorine and proper sewage Active immunization Passive immunization

Hepatitis E virus
Unclassified genus Feco-oral route, water borne Endemic in tropical countries IP: 40 days HIGH MORTALITY RATE IN PREGNANT WOMAN No chronicity Detect anti HEV antibodies and HEV-RNA in serum Same prevention and control as hepatitis A

Hepatitis B virus
Hepadnavirus Icosahendral nucleocapsid Partially double-stranded circular DNA genome Outer shell: HBsAg Inner core: Hbc Ag Secreted in soluble form: HBeAg EM of serum: spherical particles, filamentous particles and complete virions (Dane particle)

Epidemiology and transmission

High titre are present in blood and serum 1. Percutaneous Blood transfusion Contaminated syringes and needles Improperly sterilized instrument Razor and tooth brush sharing Needle stick injuries 2. Sexual transmission 3. Perinatal transmission

Clinical features
IP: 10-12 weeks Many asymptomatic Outcome: Adult: 90-95% recover completely Infected infant: chronic carries Chronic: can lead to cirrhosis, liver failure and death CHRONIC: HIGH RISK OF HCC HBV Vaccine

Virologic and serologic events

First appearance: HBs Ag Viremic stage: HBV DNA and HBE Ag HBsAg , appears 2-6 weeks before clinical and biochemical evidence, throughout the course, disappearr by 6 months after exposure Viral replication: IgM specific anti HBc Window phase: disappearance of Hbs Ag. After that, antibody to HbsAg is detected Start of resolution of disease: anti Hbe

Acute phase with recovery

 HBV chronic carriers: Hbs Ag persists for more than 6 months in thepresence of HbeAg or anti-Hbe. Low titres of IgM anti-Hbc are found in the sera of most chronic carriers. Lab: ELISA: HBV antigen and antibodies PCR: HBV DNA

Interpretation of the result

1. 2. 3. 4. serologic: four phase of HBV infection Immunization: anti-Hbs Transmissibility: HbeAg Infectious virion present: Viral DNA

Test

acute phase Positive Negative Positive

Window phase Negative Negative Positive

HBs Ag Anti-Hbs Anti-Hbc

Complete Chronic recovery carrier state Negative Positive Positive Positive Negative Positive

Prevention and control

1. Hepatitis B vaccine Prevent consequence Dose: 0,1,6 Plasma derived HBs Ag All infant, health care personnel, on transfusion, dialysis 2. Hepatitis B immunoglobulin (simultenously) - Soon after exposure - Infants to HBV positive mother, exposed person

Hepatitis D virus
Defective virus, uses Hbs Ag as envelope (HBV is helper virus) Blood borne virus Two types: Coinfection: both at same time Superinfection: of chronically infected HBV

Outcome: Coinfected: more severe that HBV alone, but incidence of chronic hepatitis is about the same Superinfected: much more severe, higher incidence of chronic hepatitis Lab: ELISA: HD Ag, IgM and anti HD antibodies PCR: HD-RNA

Hepatitis C vaccine
Flaviviridae 6 genotypes, not correlated with clinical disease, differ in response to antiviral therepy. Egypt: 4a Percutaneous or permucosal

 Appearance of anti-HCV antibodies: 8-9 weeks HCV RNA: 1-3 weeks after exposure. The means of diagnosis in seronegative patients Chronic hepatitis: serum ALT fluctuate overtime and maybe intermittently normal. HCV RNA may persists for decades

 Outcome: 70-90% chronic HCV infection Resembles hepatitis B as regards predisposition to chronic liver disease, cirrhosis and HCC. End stage liver disease associated with HCV is most common indication for liver transplantation.

Lab diagnosis
1. ELISA: detect antibodies to HCV, consider: Early seronegative phase: negative result Positive: acute, chronic, resolved? False positive can occur. Confirmed by : RIBA. If positive, test for viral RNA for active disease. - Poor serologic response in some patient. Test for HCV RNA.

2. RT-PCR, for derection of HCV RNA - Active disease - Early seronegative - Poor serologic patients Acute self limiting: dissappear (resolved) Measure viral load: response to antiviral therapy (quantitative PCR)

Hepatitis
Diffuse inflammation of parenchyma Causes: Infective Metabolic Autoimmune Chemicals drugs

1.Hepatotropic - most common form - A, B, C, D, E, G 2. Systemic

Clinicopathological syndromes
1. Subclinical asymptomatic, any type 2. Acute viral hepatitis any type 3. Chronic viral hepatitis HBV, HCV, HDV. NEVER HAV and HEV 4. Carrier state mainly HBV. NEVER HAV, HEV 5. Fulminant hepatitis HEV among pregnant females

Clinical course of acute hepatitis

1. HAV - Most undergo complete recovery 2. HBV - Most (>90%) complete recovery - 1-2% chronic hepatitis 3. HCV - >70% progress to chronic hepatitis - <30% undergo recovery - Few develop fulminant

4. HDV - coinfection: 90% undergo recovery 3-4% develop fulminat Rare progress to chronic hepatitis - Superinfection 10-15%: recovery 80%: chronic hepatitis 7-10%: fulminant 5. HEV - Most undergo complete recovery - Pregnant females: fulminant (20%) - No chronic or carrier state

CHRONIC VIRAL HEPATITIS

Symptomatic, biochemical, serological evidence of inflammatory hepatic disease with histologically documented without improvement, more than 6 months Mainly: HCV >70%, HDV (80% superinfection) and some HBV

CARRIER STATE
Not manifest symptoms, but persistent antigenemia(circulating infectious virus particles), more than 6 months with normal transaminases and no clinical symptoms. Mainly: HBV (adults infected by HBV and nonimmunized infants born to infected mother) Increased risk of HCC